Copyright ©The Author(s) 2020.
World J Gastroenterol. Jul 28, 2020; 26(28): 4076-4093
Published online Jul 28, 2020. doi: 10.3748/wjg.v26.i28.4076
Table 1 Non-gastric manifestations of Helicobacter pylori and their suggested mechanisms of pathophysiology
Non-gastric manifestationMechanisms of pathology suggested to be correlated
Allergic diseasesHygiene hypothesis[9,96]
Alzheimer’s diseaseVitamin B12 deficiency leading to increased concentrations of homocysteine[109]
Anormal hyperphosphorylation of the TAU protein caused by H. pylori infection[109]
ApoE polymorphism[110]
AsthmaTreg pattern, suppressing Th-2-mediated allergic response[94]
Atherosclerosis and myocardial infarctionStimulation of foam production inside macrophages, contributing to the magnification of the atherosclerotic plaque and arterial dysfunction[122]
B12 deficiencyStill to be clarified, but proven to be independent of gastric atrophy and bleeding that impair their dietary absorption[49]
CholelithiasisPresence of H. pylori infected bile[43,44]
Coronary arterial disease/systemic arterial stiffnessIncreased levels of homocysteine[132].
Gastroesophageal reflux diseaseHyperacidity[25]
Diabetes mellitusIncreased cytokine production; phosphorylation of serine residues from the insulin receptor substrate[136]
Hepatic carcinomaInflammatory, fibrotic and, consequently, necrotic process[37,38]
Idiopathic thrombocytopenic purpura (ITP)CagA may stimulate the synthesis of anti-CagA antibodies that cross-react with platelet surface antigens causing ITP[74,75]
Inflammatory bowel diseaseReduced intestinal inflammation through release of IL-18 and development of FoxP3-positive regulatory T cells[16-18]
Neutrophil-activating protein reducing inflammation through Toll-like receptor 2 and IL-10 stimulation[19,20]
Iron deficiency anemiaStill to be clarified, but proven to be independent of gastric atrophy and bleeding that impair their dietary absorption[49]
Relationship with growth disorders in children[52,53]
Multiple sclerosisHygiene hypothesis[9]
Inhibitory induction of H. pylori over the Th1 and Th17 immune response[103]
Non-alcoholic fatty liver diseaseH. pylori induced insulin resistance[32]
Reduced production of adiponectin[33]
Liver inflammation[34,35]
Ophthalmic manifestationsSystemic inflammatory status; increased oxidative stress; mitochondrial dysfunction; damage to DNA[82]
Parkinson’s diseaseIncreased synthesis of 1-methyl-4-phenyl-1,2,36-tetrahydropyridine[118]
Reduced levodopa absorption[118]
Table 2 Levels of evidence of the risk relationship between Helicobacter pylori infection and each non-gastroduodenal manifestation
ManifestationYear of publication1Ref.1Level of evidence
Alopecia areata2017Behrangi et al[72]III
Alzheimer’s disease2016Shindler-Itskovitch et al[107]II
2020Fu et al[108]II
Arterial hypertension2018Wan et al[127]III
Asthma2013Wang et al[90]II
2017Chen et al[91]III
Atherosclerosis2019Iwai et al[124]III
B12 deficiency2000Kaptan et al[47]I
2018Mwafy et al[48]III
Central serous chorioretinopathy2006Cotticelli et al[88]IV
Cholecystitis and cholelithiasis2015Guraya et al[43]II
2018Tsuchiya et al[41]III
2018Cen et al[44]III
Coronary artery disease2016Sun et al[131]II
Diabetes mellitus2019Chen et al[135]III
Gastroesophageal reflux disease2016Wang et al[26]II
Glaucoma2018Zeng et al[83]III
2002Kountouras et al[84]III
Guillain-Barré syndrome2020Dardiotis et al[120]III
Halitosis2017HajiFattahi et al[29]III
2019Anbari et al[30]III
Hepatic carcinoma2017Huang et al[39]III
Idiopathic thrombocytopenic purpura2018Kim et al[78]II
Inflammatory bowel disease2017Castaño-Rodríguez et al[13]III
2019Lin et al[14]III
Iron deficiency anemia2018Mwafy et al[48]III
Myocardial infarction2015Liu et al[125]III
Multiple sclerosis2007Li et al[100]III
2016Jaruvongvanich et al[101]III
2016Yao et al[102]III
Non-alcoholic fatty liver disease2019Liu et al[36]II
Parkinson’s disease2020Wang et al[118]III
Psoriasis2019Yu et al[67]II
2017Mesquita et al[64]III
Rosacea2017Saleh P et al[59]III
2017Jørgensen et al[62]III